MF-Tricyclic Inhibits Growth of Experimental Abdominal Aortic Aneurysms

W. Brent Keeling, Amy E. Hackmann, Mary E. Colter, Patrick A. Stone, Brad L. Johnson, Martin R. Back, Dennis F. Bandyk, Murray L. Shames

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Experimental abdominal aortic aneurysm (AAA) development can be pharmacologically suppressed by inhibiting matrix metalloproteinase-9 (MMP-9). Cyclooxygenase-2 (COX-2) inhibitors are potent anti-inflammatory agents that have been demonstrated to inhibit experimental aneurysm development. We hypothesized that treatment with MF-tricyclic, a selective COX-2 inhibitor, incorporated into rodent chow would inhibit aneurysm development in a rat AAA model. Methods: Twelve male Sprague Dawley rats underwent induction of experimental AAA using intra-aortic porcine elastase infusion. Six rats received control feed, and six received MF-tricyclic rodent chow for a period of 14 days. Aortic diameters were measured pre- and postinfusion as well as at harvest. Aortic tissue samples were evaluated by real-time polymerase chain reaction (RT-PCR) for MMP-9, by immunohistochemistry for elastin. Results: Elastase infusion produced AAA in all untreated rats. At 14 days MF-tricyclic-treated rats had significantly reduced aortic diameter (1.9 ± 0.1 mm versus 2.4 ± 0.0 mm, P = 0.00001). Percent increase in aortic diameter was also significantly less in animals receiving MF-tricyclic (65.7 ± 8.5% versus 132.3 ± 7.3%, P = 0.0001). RT-PCR demonstrated a decrease in the mean expression of MMP-9 in the treated animals (0.414 ng of RNA versus 1.114 ng of RNA) (P = 0.07). Sections stained for elastin demonstrated preserved elastin integrity in MF-tricyclic treated aortas. Conclusions: COX-2 inhibition helps to retard the growth of experimental AAAs possibly through inhibition of MMP-9. Experimentally treated animals demonstrated smaller aortic diameters and lower levels of tissue MMP-9 when compared to untreated animals. Selective COX-2 inhibition may offer an additional method to pharmacologically inhibit AAAs.

Original languageEnglish (US)
Pages (from-to)192-195
Number of pages4
JournalJournal of Surgical Research
Volume141
Issue number2
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 9
Abdominal Aortic Aneurysm
Elastin
Growth
Cyclooxygenase 2 Inhibitors
Pancreatic Elastase
Cyclooxygenase 2
Aneurysm
Real-Time Polymerase Chain Reaction
Rodentia
RNA
Sprague Dawley Rats
Aorta
Anti-Inflammatory Agents
Swine
Immunohistochemistry
3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2(5H)-furanone

Keywords

  • CaM
  • CV159
  • ex vivo EPR
  • hepatic IR injury
  • in vivo EPR

ASJC Scopus subject areas

  • Surgery

Cite this

Keeling, W. B., Hackmann, A. E., Colter, M. E., Stone, P. A., Johnson, B. L., Back, M. R., ... Shames, M. L. (2007). MF-Tricyclic Inhibits Growth of Experimental Abdominal Aortic Aneurysms. Journal of Surgical Research, 141(2), 192-195. https://doi.org/10.1016/j.jss.2006.12.544

MF-Tricyclic Inhibits Growth of Experimental Abdominal Aortic Aneurysms. / Keeling, W. Brent; Hackmann, Amy E.; Colter, Mary E.; Stone, Patrick A.; Johnson, Brad L.; Back, Martin R.; Bandyk, Dennis F.; Shames, Murray L.

In: Journal of Surgical Research, Vol. 141, No. 2, 01.08.2007, p. 192-195.

Research output: Contribution to journalArticle

Keeling, WB, Hackmann, AE, Colter, ME, Stone, PA, Johnson, BL, Back, MR, Bandyk, DF & Shames, ML 2007, 'MF-Tricyclic Inhibits Growth of Experimental Abdominal Aortic Aneurysms', Journal of Surgical Research, vol. 141, no. 2, pp. 192-195. https://doi.org/10.1016/j.jss.2006.12.544
Keeling, W. Brent ; Hackmann, Amy E. ; Colter, Mary E. ; Stone, Patrick A. ; Johnson, Brad L. ; Back, Martin R. ; Bandyk, Dennis F. ; Shames, Murray L. / MF-Tricyclic Inhibits Growth of Experimental Abdominal Aortic Aneurysms. In: Journal of Surgical Research. 2007 ; Vol. 141, No. 2. pp. 192-195.
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abstract = "Background: Experimental abdominal aortic aneurysm (AAA) development can be pharmacologically suppressed by inhibiting matrix metalloproteinase-9 (MMP-9). Cyclooxygenase-2 (COX-2) inhibitors are potent anti-inflammatory agents that have been demonstrated to inhibit experimental aneurysm development. We hypothesized that treatment with MF-tricyclic, a selective COX-2 inhibitor, incorporated into rodent chow would inhibit aneurysm development in a rat AAA model. Methods: Twelve male Sprague Dawley rats underwent induction of experimental AAA using intra-aortic porcine elastase infusion. Six rats received control feed, and six received MF-tricyclic rodent chow for a period of 14 days. Aortic diameters were measured pre- and postinfusion as well as at harvest. Aortic tissue samples were evaluated by real-time polymerase chain reaction (RT-PCR) for MMP-9, by immunohistochemistry for elastin. Results: Elastase infusion produced AAA in all untreated rats. At 14 days MF-tricyclic-treated rats had significantly reduced aortic diameter (1.9 ± 0.1 mm versus 2.4 ± 0.0 mm, P = 0.00001). Percent increase in aortic diameter was also significantly less in animals receiving MF-tricyclic (65.7 ± 8.5{\%} versus 132.3 ± 7.3{\%}, P = 0.0001). RT-PCR demonstrated a decrease in the mean expression of MMP-9 in the treated animals (0.414 ng of RNA versus 1.114 ng of RNA) (P = 0.07). Sections stained for elastin demonstrated preserved elastin integrity in MF-tricyclic treated aortas. Conclusions: COX-2 inhibition helps to retard the growth of experimental AAAs possibly through inhibition of MMP-9. Experimentally treated animals demonstrated smaller aortic diameters and lower levels of tissue MMP-9 when compared to untreated animals. Selective COX-2 inhibition may offer an additional method to pharmacologically inhibit AAAs.",
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AU - Hackmann, Amy E.

AU - Colter, Mary E.

AU - Stone, Patrick A.

AU - Johnson, Brad L.

AU - Back, Martin R.

AU - Bandyk, Dennis F.

AU - Shames, Murray L.

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N2 - Background: Experimental abdominal aortic aneurysm (AAA) development can be pharmacologically suppressed by inhibiting matrix metalloproteinase-9 (MMP-9). Cyclooxygenase-2 (COX-2) inhibitors are potent anti-inflammatory agents that have been demonstrated to inhibit experimental aneurysm development. We hypothesized that treatment with MF-tricyclic, a selective COX-2 inhibitor, incorporated into rodent chow would inhibit aneurysm development in a rat AAA model. Methods: Twelve male Sprague Dawley rats underwent induction of experimental AAA using intra-aortic porcine elastase infusion. Six rats received control feed, and six received MF-tricyclic rodent chow for a period of 14 days. Aortic diameters were measured pre- and postinfusion as well as at harvest. Aortic tissue samples were evaluated by real-time polymerase chain reaction (RT-PCR) for MMP-9, by immunohistochemistry for elastin. Results: Elastase infusion produced AAA in all untreated rats. At 14 days MF-tricyclic-treated rats had significantly reduced aortic diameter (1.9 ± 0.1 mm versus 2.4 ± 0.0 mm, P = 0.00001). Percent increase in aortic diameter was also significantly less in animals receiving MF-tricyclic (65.7 ± 8.5% versus 132.3 ± 7.3%, P = 0.0001). RT-PCR demonstrated a decrease in the mean expression of MMP-9 in the treated animals (0.414 ng of RNA versus 1.114 ng of RNA) (P = 0.07). Sections stained for elastin demonstrated preserved elastin integrity in MF-tricyclic treated aortas. Conclusions: COX-2 inhibition helps to retard the growth of experimental AAAs possibly through inhibition of MMP-9. Experimentally treated animals demonstrated smaller aortic diameters and lower levels of tissue MMP-9 when compared to untreated animals. Selective COX-2 inhibition may offer an additional method to pharmacologically inhibit AAAs.

AB - Background: Experimental abdominal aortic aneurysm (AAA) development can be pharmacologically suppressed by inhibiting matrix metalloproteinase-9 (MMP-9). Cyclooxygenase-2 (COX-2) inhibitors are potent anti-inflammatory agents that have been demonstrated to inhibit experimental aneurysm development. We hypothesized that treatment with MF-tricyclic, a selective COX-2 inhibitor, incorporated into rodent chow would inhibit aneurysm development in a rat AAA model. Methods: Twelve male Sprague Dawley rats underwent induction of experimental AAA using intra-aortic porcine elastase infusion. Six rats received control feed, and six received MF-tricyclic rodent chow for a period of 14 days. Aortic diameters were measured pre- and postinfusion as well as at harvest. Aortic tissue samples were evaluated by real-time polymerase chain reaction (RT-PCR) for MMP-9, by immunohistochemistry for elastin. Results: Elastase infusion produced AAA in all untreated rats. At 14 days MF-tricyclic-treated rats had significantly reduced aortic diameter (1.9 ± 0.1 mm versus 2.4 ± 0.0 mm, P = 0.00001). Percent increase in aortic diameter was also significantly less in animals receiving MF-tricyclic (65.7 ± 8.5% versus 132.3 ± 7.3%, P = 0.0001). RT-PCR demonstrated a decrease in the mean expression of MMP-9 in the treated animals (0.414 ng of RNA versus 1.114 ng of RNA) (P = 0.07). Sections stained for elastin demonstrated preserved elastin integrity in MF-tricyclic treated aortas. Conclusions: COX-2 inhibition helps to retard the growth of experimental AAAs possibly through inhibition of MMP-9. Experimentally treated animals demonstrated smaller aortic diameters and lower levels of tissue MMP-9 when compared to untreated animals. Selective COX-2 inhibition may offer an additional method to pharmacologically inhibit AAAs.

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KW - hepatic IR injury

KW - in vivo EPR

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